Triple Therapy With Aspirin, Prasugrel and Vitamin K Antagonists in Patients With Drug Eluting Stent Implantation and an Indication for Oral Anticoagulation

Study Questions:

What is the safety and efficacy of prasugrel as an alternative to clopidogrel in patients with triple therapy?


The investigators analyzed a consecutive series of 377 patients who underwent drug-eluting stent (DES) implantation and had an indication for oral anticoagulation between February 2009 and December 2011, and were treated with a 6-month regimen of aspirin and oral anticoagulation with either prasugrel or clopidogrel. The primary endpoint was a composite of Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding at 6 months. The secondary endpoint was a composite of death, MI, ischemic stroke, or definite stent thrombosis. Both, unadjusted and adjusted risk estimates were calculated by Cox analysis.


Twenty-one patients (5.6%) received prasugrel instead of clopidogrel. These patients had a higher risk profile at baseline and the majority had high platelet reactivity to clopidogrel. TIMI major and minor bleeding occurred significantly more often in the prasugrel as compared to the clopidogrel group (6 [28.6%] vs. 24 [6.7%]; unadjusted hazard ratio [HR] 4.6, 95% confidence interval [CI] 1.9-11.4, p < 0.001; adjusted HR 3.2, 95% CI 1.1-9.1, p = 0.03). There was no significant difference regarding the combined ischemic secondary endpoint (2 [9.5%] vs. 25 [7.0%]; unadjusted HR 1.4, 95% CI 0.3-6.1, p = 0.61).


The authors concluded that the substitution of prasugrel for clopidogrel in patients needing triple therapy increases the risk of bleeding.


This study suggests that prasugrel therapy is associated with an increased rate of TIMI major and minor bleeding as compared to clopidogrel in patients who require oral anticoagulation after DES. There was no significant difference regarding the composite ischemic endpoint between both groups. Given the observational nature of the study and small number of patients in the prasugrel group, adequately powered randomized trials are needed to define the role of newer adenosine diphosphate receptor antagonists in this setting. At this time, there appears to be no significant benefit to substituting clopidogrel with a more potent agent for those on triple therapy.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Thiophenes, Purinergic P2Y Receptor Antagonists

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